THE IMPACT OF MASS AZITHROMYCIN TREATMENTS ON ANTIBIOTIC RESISTANCE AND THE DISTRIBUTION OF S. PNEUMONIAE SEROTYPES IN ETHIOPIA Público

Abstract

Background: Trachoma is one of the leading preventable causes of blindness in the
developing world. The World Health Organization recommends repeated annual mass
oral azithromycin treatments for entire districts where the prevalence exceeds 10%
among children aged 1-9 years old. S. pneumoniae, with more than 93 serotypes, is one
of the leading causes of child mortality in the developing world. Repeated annual mass
antibiotic treatment has raised concerns in both the development of antibiotic resistant
strains of S. pneumoniae and the change in serotype distribution. This research was
conducted to determine whether treatment with oral azithromycin and increased resistant
strains changed the distribution of seven-valent vaccine serotypes.

Methods: The study was a population-based, cluster-randomized clinical trial of quarterly
mass oral azithromycin treatments (20 mg/kg) for trachoma. Nasopharyngeal swabs were
collected from 10 children of each sentinel community. S. pneumoniae strains were
isolated and serotypes were identified. Resistance to the following antibiotics:
azithromycin, penicillin, clindamycin and tetracycline, was evaluated by MICs and
included in the analysis. Chi-square tests were performed to compare serotype
distribution. Logistic regression was used to determine whether treatment and population
characteristics were associated with seven-valent vaccine serotypes.

Results: The difference in proportions for the most prevalent serotypes in the study (19F,
6B, 6A, 7F and 9L) at baseline and at one-year follow-up was not statistically significant
(p-value=0.58). The association between treatment and vaccine serotypes was not
statistically significant for the univariate and multivariate analyses (OR=1.02, 95%
CI=0.49-2.15, OR=1.14, 95% CI=0.42-3.08, respectively). Azithromycin resistance
increased from 5.8% at baseline to 60.7% at one-year follow up (p= <0.0001). The
multivariate analysis included gender, trachoma, age, azithromycin-, penicillin-,
clindamycin- and tetracycline-resistance. Azithromycin resistance was associated with
non-vaccine serotypes (OR=29.59, 95% CI=3.01-291.17), while penicillin-, clindamycin-
and tetracycline-resistance were associated with vaccine serotypes after adjusting for
other covariates (OR=4.98, 95% CI=0.996-24.87; OR=57.91, 95% CI=5.13-653.83;
OR=5.07, 95% CI=1.51-16.98, respectively).

Conclusion: Mass treatments with oral azithromycin did not change the overall
distribution of serotypes but did increase antibiotic resistance. Azithromycin resistance
selects for non-vaccine serotypes, while resistance to penicillin, clindamycin and
tetracycline were associated with vaccine serotypes.

Table of Contents

TABLE OF CONTENTS

BACKGROUND .................................................................................................................................................... 1

METHODS .........................................................................................................................................................12

RESULTS ..........................................................................................................................................................22

DISCUSSION .....................................................................................................................................................28

REFERENCES .....................................................................................................................................................35

FIGURES ...........................................................................................................................................................42

TABLES ........................................................................................................................................................... 46

46

About this Master's Thesis

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School	Rollins School of Public Health
Department	Epidemiology
Subfield / Discipline	Global Epidemiology - MPH & MSPH
Degree	MPH
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Public Health Health Sciences, Epidemiology
Palabra Clave	Ethiopia antibiotic resistance S. pneumoniae azithromycin treatment
Committee Chair / Thesis Advisor	Klugman, Keith P, Emory University
Committee Members	Vidal Graniel, Jorge Eugenio, Emory University
Partnering Agencies	Emory University schools, faculty or affiliated programs University, college or educational institution (other than Emory)

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